Although much is known about the molecular basis of vision and olfaction, almost nothing is known about the molecular biology of taste. Humans and flies have four basic taste modalities, sweet, sour, bitter and salty. This grant focuses on a molecular genetic dissection of taste in Drosophila melanogaster, a model system particularly well suited for a genetic dissection of this process in vivo. It is expected that results obtained from these studies will be important in elucidating the molecular basis of taste, and will help our understanding of sensory signaling in general. We will: (1) Develop a comprehensive genetic screen to isolate mutations affecting taste cell function, including sweet, bitter and salty pathways. (2) We will screen for autosomal recessive mutations so as to generate an extensive genetic database for detailed analysis and (3) characterize the mutants genetically and physiologically. In particular, we will developed a preparation suitable for physiological analysis and use electrophysiological recording together with genetic epistasis to localize the site of action of the defective genes.(4) We will isolate the defective genes and determine their entire nucleotide sequence. Wild type and mutant copies will be introduced back into flies by P-element mediated germ line transformation and tested for rescuing and/or induction of taste cell dysfunction. We will study in detail those sequences which based on their patterns of expression and genetic and physiological criteria most warrant further investigation. We will define the normal function of the affected loci, and determine the molecular basis of the defect. Finally, (5) we will use the Drosophila genes to isolate the corresponding human homologs, and make those sequences available to the community working on vertebrate models.